Submissions for variant NM_002230.4(JUP):c.1913A>C (p.Asn638Thr)

dbSNP: rs561484928

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486345	SCV000574071	uncertain significance	not provided	2017-03-15	criteria provided, single submitter	clinical testing	The N638T variant has not been published as pathogenic or been reported as benign to our knowledge. The N638T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. Though the N638T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae	RCV001306875	SCV001496260	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2022-03-09	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 424280). This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 638 of the JUP protein (p.Asn638Thr).